The program is concerned with the basic events taking place at the cholinergic receptor and consists of projects focused on the reactions involved in the activation of the receptor and its subsequent restoration to the resting state. Evidence has been found that agonists act at receptors not by simple combination but by displacing bivalent calcium or magnesium ions from them by stoichiometric ion exchange. The evidence is being analyzed by the application of a group of recently derived thermodynamically valid ion exchange equations to the competition between potent ligands and the bivalent ionorganic ions at particulate preparations of the receptors. A new potent, electron-dense curariform compound, osmarine, containing two osmium atoms is being used to study the electron microscopic ultrastructure of the receptor arrangement. The optical properties of individual synaptic membranes from torpedo electroplaxes are being studied to detect conformational changes produced by the actions of depolarizing ligands. BIBLIOGRAPHIC REFERENCES: Charles E. Spivak and Dermot B. Taylor: "A filter assay for binding of labeled ligands to membrane-bound receptors." Anal. Biochem. 77:274-279 (1977).